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Updated: Jun 2, 2026
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Investigating the Anticancer Promise of Synthesized Methylated N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides:
Batool Al-Lahowani1, Tahrer Al-Bo Aswad1, Rima Hajjo1
1Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Abstract:
Cancer is a multifaceted disease that places a significant burden on healthcare systems and economies, driving the urgent need for novel therapeutic agents to curb its prevalence and impact. Thirty-three analogues of N-substituted-7-and 8-methyl-4-hydroxy-2-quinolone-3-carboxamides were synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. The analogues displayed potential cytotoxicity against human colon cancer (HCT-116) and epithelial colorectal adenocarcinoma (Caco-2) cells. Compounds bearing a phenyl ring tailored with o-CF3 (26) and a phenyl ring substituted with o-COOH and p-CH3 (29) exert preferential inhibitory activity against HCT-116 with IC50s 9.4 and 7.8 μM. The bioinformatics calculations interpret the selectivity of analogues against HCT-116. The principal component analysis (PCA) discloses that the analogues are regarded as lead-like and nominated for hit-to-lead and lead optimization stages of drug discovery. Docking studies illustrate that analogues accommodate the kinase domain of PI3Kα and engage with key binding residues. The promising outcome of this work emphasizes the significance of this scaffold as anticancer agents.
Insights
Novel quinolone carboxamide analogues show potent anticancer activity against colon cancer cells. Specific compounds exhibit preferential inhibition, indicating promise for drug discovery and development.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Oncology
Background:
- Cancer poses a significant global health and economic burden.
- There is a continuous need for developing new anticancer therapeutics.
- Quinolone derivatives have shown potential in various therapeutic areas.
Purpose of the Study:
- To synthesize and evaluate novel N-substituted-7-and 8-methyl-4-hydroxy-2-quinolone-3-carboxamide analogues as potential anticancer agents.
- To identify specific analogues with potent and selective cytotoxicity against colorectal cancer cell lines.
- To explore the drug-like properties and binding interactions of these analogues.
Main Methods:
- Synthesis of 33 N-substituted-7-and 8-methyl-4-hydroxy-2-quinolone-3-carboxamide analogues.
- Characterization using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis.
- Cytotoxicity assays against HCT-116 and Caco-2 cells, bioinformatics analysis, principal component analysis (PCA), and molecular docking studies.
Main Results:
- Analogues demonstrated cytotoxicity against human colon cancer (HCT-116) and epithelial colorectal adenocarcinoma (Caco-2) cells.
- Compounds 26 (o-CF3 phenyl) and 29 (o-COOH, p-CH3 phenyl) showed preferential inhibition against HCT-116 (IC50s 9.4 and 7.8 μM, respectively).
- Bioinformatics and PCA indicated lead-like properties, suitable for hit-to-lead optimization. Docking revealed interactions with the PI3Kα kinase domain.
Conclusions:
- The synthesized quinolone carboxamide analogues represent a promising scaffold for anticancer drug development.
- Compounds 26 and 29 exhibit significant potential as targeted therapies for colon cancer.
- Further optimization and investigation are warranted to advance these compounds towards clinical application.
